Fig 1.
CONSORT statement 2010 flow diagram.
The number of participants enrolled, randomized, allocated to study medication, followed-up and analyzed is shown. Study participants who progressed to the endpoint of the study (CD4 < 200 or CDC stage-C disease) received HAART. In some cases, study participants also received HAART when they progressed to CD4 < 350 in combination with WHO stage 3-disease. This was in accordance to the National Tanzanian treatment recommendations Update in 2008 (1 case in the placebo arm and 3 cases in the prednisolone arm). In addition, one patient in the placebo arm and 2 study participants in the prednisolone arm received HAART without fulfilling either the study endpoint or the criteria listed in the National Treatment recommendation update.
Table 1.
Patient characteristics.
Fig 2.
Study drug adherence and loss to follow-up.
A, B: Study drug adherence calculated from pill counts of returned, unused study medication in female (A) and male (B) study participants. P-values were calculated by 2way ANOVA C: Loss to follow-up during the two-year study. P value was calculated by log-rank (Mantel-Cox) analysis.
Fig 3.
CD4 counts of study participants with loss of follow-up.
A: Baseline (BL) CD4 counts from study participants who were later lost to follow up (lost) and who fulfilled (fulfilled) the study. P value was calculated by Mann-Whitney test. B: CD4 counts prior to loss to follow up (loss) or to progression to the primary endpoint (HAART). Red bars (placebo) and blue bars (prednisolone) represent medians. P values were calculated by Kruskal-Wallis test with multiple comparisons.
Fig 4.
Effects of prednisolone on HIV disease progression: Primary Study Endpoint.
Kaplan-Meyer estimate of progression to combined study endpoint (onset of CDC stage-C-condition or drop of CD4 counts below 200) within the intent-to-treat (ITT) population (A) or the per protocol (PP) population (B). C: Progression to AIDS-defining condition. All study participants who received HAART, but did not reach the study endpoint were censored for the KM analysis. D-F and G-I: Post-hoc analyses for female study participants (D-F) and for male study participants (H-I) for progression to combined endpoint within the ITT population (D, G), progression to combined endpoint within the PP population (E, H), and progression to AIDS-defining condition (F, I). A-I: P values were calculated by log-rank (Mantel-Cox) analysis.
Table 2.
Clinical endpoints and other reasons for initiating HAART.
Fig 5.
Disease progression in male and female study participants.
Kaplan-Meyer estimate of progression to combined study endpoint (onset of CDC stage-C-condition or drop of CD4 counts below 200) within the intent-to-treat (ITT) population of study participants treated with placebo (A) or prednisolone (B) stratified by sex. P values were calculated by log-rank (Mantel-Cox) analysis.
Fig 6.
Progression to HAART as treated.
Kaplan-Meyer estimate of progression to HAART as treated within the intent-to-treat (ITT) population (A) or the per protocol (PP) population (B). Separate analyses for female study participants (B, E) and for male study participants (C, F) for progression to HART as treated. P values were calculated by log-rank (Mantel-Cox) analysis.
Fig 7.
Number of study participants at risk within the intent-to-treat (ITT) population (A) or the per protocol (PP) population (B). Separate analyses for female study participants (C, D) and for male study participants (E, F).
Fig 8.
Effects of prednisolone on CD4 counts and CD4/CD8 ratio.
A: Mean CD4 ± S.D. P-values were determined by 2way ANOVA. B: Mean CD4 changes ± S.D. relative to baseline and linear regression of the data. 2-year gains/losses were calculated from slope of linear regression. C: Mean ± S.D. CD4/CD8-ratio and linear regression. B, C: P values on the right indicate non-zero hypotheses for the slope. P-value on the left for difference between the two data sets was calculated by 2way ANOVA. D-F and G-I: Post-hoc analyses for female study participants (D-F) and for male study participants (H-I) for absolute CD4 counts (D, G), CD4 relative CD4 changes (E, H), and CD4/CD8 ratio (F, I).
Fig 9.
Effects of prednisolone on immune activation and HIV viral load.
A, E, I: Concentration of sCD14 was determined by ELISA from n = 134 (placebo) and n = 136 (prednisolone) available plasma samples collected at baseline, 3, 6 and 12 months. A: all sexes, E: females (nPlac = 106, nPred = 110), I: males (nPlac = 28, nPred = 26). B, F, J: Concentration of sUPAR was determined by ELISA from n = 122 (placebo) and n = 124 (prednisolone) available plasma samples collected at baseline, 3, 6 and 12 months. B: all sexes, F: females (nPlac = 95, nPred = 102), J: males (nPlac = 27, nPred = 22). A, B, E, F, I, J: Data as means ± S.D. P-values were determined by 2-way ANOVA (difference between the two treatments over the whole time period) or by Wilcoxon matched-pairs signed test (changes between Baseline and month 12). C, G, K: CD38/HLA-DR expression was determined by flow cytometry from n = 22 (placebo) and n = 30 (prednisolone) available frozen PBMC samples collected at baseline and 12 months. C: all sexes, G: females (nPlac = 19, nPred = 27), K: males (nPlac = 3, nPred = 3). P-values were determined by Wilcoxon matched-pairs signed test (changes between Baseline and month 12). D, H, L: HIV viral load was determined from n = 86 (placebo) and n = 80 (prednisolone) available plasma pairs at baseline and month 12. D: all sexes, H: females (nPlac = 70, nPred = 66), L: males (nPlac = 16, nPred = 14). P-values were determined by Wilcoxon matched-pairs signed test (changes between Baseline and month 12) and by Mann-Whitney test (comparison of month 12 placebo versus month 12 prednisolone).
Table 3.
Adverse Events.